This is a multidisciplinary, collaborative research program bringing together investigators from several institutions to work across technology and disciplinary boundaries. The group shares a common interest in vascular biology, particularly in the eye, and specifically in the application of modern optical technology to answer critical questions related to vascular biology. The technology platform will be based on the scanning laser ophthalmoscope and the real-time in vivo confocal microscope previously developed at Schepens Eye Research Institute and at the Wellman Laboratories of Photomedicine. The existing technology will be enhanced with new development to improve image resolution, contrast, sensitivity, methods for quantification, and flexibility of imaging in living animals. Specific questions to be addressed include: 1. What are the cellular processes governing normal vascular development and stabilization? 2. What are the factors governing angiogenesis, Iymphangiogenesis, and immune cell trafficking? 3. What are the cellular mechanisms for the development of sickle cell and diabetic retinopathy? 4. Can we visualize early changes in the retinal pigment epithelium noninvasively in vivo? 5. Can we detect circulating cells in vivo without drawing blood? Is the number of circulating tumor cells a good predictor for tumor burden and response to therapy? Imaging at the cellular level will enable biologists to study problems in living animals over time, gaining physiological insights beyond what can be obtained by classic static measurement (histology, immunocytochemistry, etc.), substantially reducing the number of animals required to answer these critical questions.